chr2-219213842-G-C

Position:

chr2-219213842-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005689.4(ABCB6):c.1562C>G(p.Thr521Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00453 in 1,614,146 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 12 hom., cov: 33)

Exomes 𝑓: 0.0042 ( 23 hom. )

Consequence

ABCB6
NM_005689.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 1.83

Variant links:

Genes affected

ABCB6 (HGNC:47): (ATP binding cassette subfamily B member 6 (LAN blood group)) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. ABC proteins transport various molecules across extra- and intra-cellular membranes. This protein is a member of the heavy metal importer subfamily and plays a role in porphyrin transport. This gene is the molecular basis of the Langereis (Lan) blood group antigen and mutations in this gene underlie familial pseudohyperkalemia and dyschromatosis universalis hereditaria. [provided by RefSeq, Mar 2017]

ABCB6 links:

ENSG00000284820 (HGNC:):

ENSG00000284820 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007683784).

BP6

Variant 2-219213842-G-C is Benign according to our data. Variant chr2-219213842-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 445477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219213842-G-C is described in Lovd as [Benign]. Variant chr2-219213842-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00742 (1130/152302) while in subpopulation AFR AF= 0.0176 (730/41560). AF 95% confidence interval is 0.0165. There are 12 homozygotes in gnomad4. There are 534 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1130 AD,BG gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB6	NM_005689.4 linkuse as main transcript	c.1562C>G	p.Thr521Ser	missense_variant	9/19	ENST00000265316.9	NP_005680.1	Q9NP58-1
ABCB6	NM_001349828.2 linkuse as main transcript	c.1424C>G	p.Thr475Ser	missense_variant	8/18		NP_001336757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ABCB6	ENST00000265316.9 linkuse as main transcript	c.1562C>G	p.Thr521Ser	missense_variant	9/19	1	NM_005689.4	ENSP00000265316.3	Q9NP58-1
ENSG00000284820	ENST00000446716.5 linkuse as main transcript	n.*3521C>G		non_coding_transcript_exon_variant	13/22	2		ENSP00000398528.1	H7C152
ENSG00000284820	ENST00000446716.5 linkuse as main transcript	n.*3521C>G		3_prime_UTR_variant	13/22	2		ENSP00000398528.1	H7C152

Frequencies

GnomAD3 genomes

AF:

0.00742

AC:

1129

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0176

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00366

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00448

Gnomad OTH

AF:

0.00576

GnomAD3 exomes

AF:

0.00382

AC:

959

AN:

250912

Hom.:

AF XY:

0.00375

AC XY:

509

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.0160

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.00456

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.000693

Gnomad NFE exome

AF:

0.00437

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00423

AC:

6190

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00410

AC XY:

2979

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0176

Gnomad4 AMR exome

AF:

0.00275

Gnomad4 ASJ exome

AF:

0.00398

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00160

Gnomad4 FIN exome

AF:

0.000862

Gnomad4 NFE exome

AF:

0.00431

Gnomad4 OTH exome

AF:

0.00584

GnomAD4 genome

AF:

0.00742

AC:

1130

AN:

152302

Hom.:

Cov.:

AF XY:

0.00717

AC XY:

534

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0176

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00448

Gnomad4 OTH

AF:

0.00617

Alfa

AF:

0.00481

Hom.:

Bravo

AF:

0.00858

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.0166

AC:

ESP6500EA

AF:

0.00395

AC:

ExAC

AF:

0.00385

AC:

468

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00540

EpiControl

AF:

0.00445

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:8

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 19, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Apr 18, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	ABCB6: BP4, BS1, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 23, 2021	See Variant Classification Assertion Criteria. -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	Jan 02, 2020	- -

Acute intermittent porphyria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Phillips Lab, Hematology, University of Utah

Aug 16, 2021

- -

Variegate porphyria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Phillips Lab, Hematology, University of Utah

Aug 16, 2021

- -

Hereditary coproporphyria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Phillips Lab, Hematology, University of Utah

Aug 16, 2021

- -

Protoporphyria, erythropoietic, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Phillips Lab, Hematology, University of Utah

Aug 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.39

T;T

MetaRNN

Benign

0.0077

T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

-0.14

N;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.46

N;.

REVEL

Uncertain

0.32

Sift

Benign

0.55

T;.

Sift4G

Benign

0.67

T;.

Polyphen

0.0

B;B

Vest4

0.72

MutPred

0.47

Gain of helix (P = 0.0425);.;

MVP

0.81

MPC

0.19

ClinPred

0.0024

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over